SAN DIEGO—Patients living with gastroesophageal reflux disease and Barrett’s esophagus have differences in their small-bowel microbiome, specifically in the amount of Helicobacter pylori, compared with people without these conditions, according to new research presented at DDW 2025.
Long-term use of proton pump inhibitors may create chemical changes in the gut, facilitating the growth of more gram-negative bacteria that can cause inflammation (World J Gastroenterol 2021;27[18]:2054-2072) and potentially leading to differences in the small-bowel microbiome of patients with GERD and BE.
To evaluate these potential differences, Amrit Kamboj, MD, an assistant professor of medicine at Cedars-Sinai, in Los Angeles, and his co-investigators, including senior author Mark Pimentel, MD, evaluated three patient populations—56 patients with GERD, 13 with BE and 372 with neither condition—assessing for small intestinal bacterial overgrowth (presentation 332). Patients were almost evenly split between men and women and were an average age of 60 years. The average body mass index for the study participants was 26 kg/m2. Patients underwent an upper endoscopy with small-bowel aspirates to assess for SIBO, and the investigators sequenced the patients’ duodenal microbial DNA. SIBO was defined as at least 103 colony-forming units/mL on MacConkey agar.
Dr. Kamboj reported that GERD and BE were not associated with SIBO, but there were specific differences between the flora within the microbiomes of the GERD and BE populations and the control group.
They found a statistically significant lower relative abundance of H. pylori in the GERD and BE groups (fold change [FC], –1.65 [P=0.03] and –5.56 [P=0.01], respectively). In addition, the patients with GERD had a higher abundance of Desulfovibrionaceae (FC, 5.50; P=4.2–36), Bilophila (FC, 6.57; P=5.56–50) and Aeromonadaceae (FC, 6.56; P=3.75–31).
Aeromonadaceae are histamine producers, Dr. Kamboj noted, and “[Desulfovibrionaceae and Bilophila] are hydrogen sulfide–producing organisms. It is unclear the exact mechanism of action as to how this may affect reflux, and more studies are needed [evaluating] the species in this group.”
The results of the analysis also show that patients with GERD had a lower abundance of Clostridiaceae (FC, –8.76; P=2.2–30). A prior study from the investigators found that that patients who frequently used PPIs had lower abundance of Clostridiaceae than those who did not (FC –88.24; P<0.001) (Dig Dis Sci 2022;67[1]:224-232). Dr. Kamboj said more studies are needed to to understand the species within this biological family and determine what mechanism of action reduces Clostridiaceae.
Dr. Kamboj noted a well-established inverse relationship between H. pylori and BE, which may be because of decreased gastric acid production that is linked with thinning of the stomach lining in these populations. However, more data that include saliva, esophageal aspirates, and eating and drinking patterns are needed to better understand the dynamics of this inverse relationship. The goal of this and further studies, he said, is to explore novel interventions and to avoid overmedicating patients with acid-suppressive medications.
Eamonn M.M. Quigley, MD, the chief of the gastroenterology division and chair of medicine in digestive health at Houston Methodist Hospital, said one of the consequences of long-term infection with H. pylori is a reduction in gastric acid production, which leads to a lower incidence of GERD. This research supports further exploration of how PPIs affect the gut microbiome and clinical outcomes, he said.
“While the number of subjects with BE was small, the microbiome changes seen in GERD, at least at genus level, were not seen in BE,” Dr. Quigley noted. “[I] would be very interested in more data on BE versus GERD in general, as BE has the potential to lead to esophageal adenocarcinoma.”
Dr. Quigley also noted that he would be curious to review microbial samples from the stomach and esophagus as opposed to the duodenum, adding that “this is clearly an area deserving of further study.”
—Karen Fischer
Dr. Kamboj reported a financial relationship with Sanofi. Dr. Quigley reported financial relationships with Atmo, Biomerica, EnteroBiotix, FoodMarble, Nimble, Novonesis and Vibrant.
This article is from the October 2025 print issue.